Blood centers, FDA enhance screening safety with advanced test study

Tammy Wright

SAN DIEGO— BLOOD CENters across America have embraced a screening test that is enabling them to detect contaminated donations earlier than ever, making the possibility of a zero-risk blood supply more of a reality.

According to the Food and Drug Administration (FDA), approximately 99 percent of blood and plasma collected in the U.S. for transfusion or for manufacture into plasma derivatives is currently being analyzed by an advanced screening method known as nucleic acid amplification testing (NAT) to detect HIV and hepatitis C (HCV).

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A technician inspects incoming donor samples from a Red Cross blood services region in preparation of Nucleic Acid Testing. Photo courtesy of the American Red Cross.

The technology is being evaluated under interim FDA Investigational New Drug (IND) applications, using minipools instead of single blood donations. The agency says it authorized a (voluntary) system-wide implementation, prior to licensing, to speed up development and application of the technology, which has been available since the early 1980s but was impractical for making blood and plasma derivatives safer until recently.

'It is a revolution of great significance because it moves the detection of potential viral and other contaminants of blood for transfusion into the realm of molecular biology,” claims Edward Tabor, associate director for Medical Affairs in the FDA's Office of Blood, during the agency's latest workshop on NAT implementation.

The key benefit associated with NAT is its ability to detect viruses earlier than current screens, which are extremely sensitive and as effective as possible at present. In simple terms, NAT looks at the genetic material of a virus as opposed to looking for antibodies, which form as an individual body's response to a virus. The test searches for these viral particles in sample pools and then labs amplify the particles in a 60-minute time period creating billions of copies called amplicons. The amplicons detect the presence of HIV or HCV.

NAT doesn't require the capacity of viral load that current serological tests need to detect the presence of disease. Its sensitivity is much greater, says Joan McAuley, technical director of United Blood Services's NAT lab (Scottsdale, AZ).

'If a person has HIV, for example, NAT can pick up its presence approximately six days after exposure. An antibody test could take two to three weeks,” she explains. 'NAT picks up HCV in about 21 days versus antibody tests which could take three months to detect its presence.”

Reducing this 'window period”—the time between when a virus infects the blood and when the body forms antibodies to it—is a major leap in improving the safety of the nation's blood supply, according to the American Red Cross. The organization estimates that only about one per million HIV donors and one per 100,000 HCV donors actually donate during the window period and test negative for the viruses on current screening tests. But, officials say the time advantage NAT technology offers will allow about four to six additional donors with HIV and about 50 donors with HCV to be detected each year.

'The numbers may seem small, but any new safety measure today is going to seem incrementally smaller than [advances made] in the past. The point is our business mission is to provide the safest possible blood supply,” says Kathy Waldman, senior project director for the Red Cross's NAT implementation program and interim CEO of its National Genome Testing Laboratory in San Diego.

Waldman says the Red Cross opened the first NAT lab in the U.S. in March 1999. Since then, it's tested slightly over four million donations, recording a 0.17 percent reactive rate using pools of 16.

America's Blood Centers (ABC; Washington, DC)—an umbrella group for community blood centers collecting one-half of the nation's blood supply—is another entity involved in NAT. The organization has 16 NAT test laboratories, including the one operated by United Blood Services. Out of 1.4 million donations tested during its first nine months of the study, ABC confirmed four HCV positives for a rate of about 1 in 340,000 and two cases of HIV.

'This is a far bigger story than people think. Under IND, we're studying the safety and effectiveness [of NAT] on a national scale. It's never been used on a wide-scale basis and under the conditions blood centers use to test donations. It is the next wave in testing,” says ABC spokesperson Melissa McMillan.

Waldman of the Red Cross agrees. 'The introduction of this technology into donor screening could help with the detection of new and emerging viruses, and once licensed, may eliminate the need for existing tests,” she says.

Both McMillan and Waldman note that NAT implementation also puts the U.S. on par with the European Union, which issued a directive requiring HCV RNA (ribonucleic acid) testing in Europe for all plasma for fractionation by July 1, 1999.

Blood centers say another residual public health benefit garnered by NAT is its ability to provide early diagnosis and referral of donors for medical treatment.

In the future, the FDA believes NAT may also permit the simultaneous detection of multiple blood-borne pathogens in one assay system. It may also have the potential to nearly eliminate the transmission of the hepatitis B virus by blood transfusion, as well as eliminate bacterial infections as a complication of transfusion and eliminate transmission of such viruses as human Parvovirus B-19 and hepatitis A, which are not affected by currently available inactivation steps in the manufacture of plasma derivatives.

'The information we're gathering with the studies will help us verify the technology's utility in the field. So far, the data is indicating that the tests are favorable for the early detection of HIV and HCV. We're trying to come to closure and determine if NAT can be put in place for indefinite future use,” says Dr. Indira Hewlett, chairman of the Laboratory of Molecular Virology at FDA's Center for Biologics (Bethesda, MD).

She anticipates licensure of NAT tests at some point, and says while sample pooling was a cost-effective way to implement NAT for donor screening, efforts are underway to develop a single-use test for NAT — the traditional mode of testing in the U.S.

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